CASE REPORTOpen Access
Cytomegalovirus infection associated with onset
of ulcerative colitis
Mitsuro Chiba1*, Toru Abe1, Satoko Tsuda1and Iwao Ono2
Background: In 2009, a trigger role of cytomegalovirus (CMV) was shown in the development of ulcerative colitis
(UC) in mice. Fifteen cases of synchronous onset of CMV colitis and UC have been reported in literature. A careful
prospective and retrospective survey identified CMV colitis in newly diagnosed UC patients at 4.5% (3/65 cases) and
8.2% (5/61 cases), respectively. This means that a majority of synchronous CMV colitis may be missed in newly
diagnosed UC patients in routine practice. Such a case is presented.
Case presentation: A 50-year-old woman, with a history of right partial mastectomy two years ago, had a
persistent high fever for 9 days, after which a thickness of the colonic wall was detected on abdominal
ultrasonography. Laboratory data showed inflammation and 2% atypical lymphocytes with the normal number of
white blood cells. Although there was no bloody stool, fecal occult blood was over 1000 ng/ml. Colonoscopy
showed diffuse inflammation in the entire large bowel and pseudomembranes in the sigmoid colon. The diagnosis
was UC with antibiotic-associated pseudomembranous colitis. Metronidazole followed by sulfasalazine resulted in
defervescence and improvement in laboratory data of inflammation. It took one month for normalization of fecal
occult blood. Endoscopic remission was simultaneously confirmed. Later, it was found that a report of positive CMV
antigenaemia (2/150,000) had been missed. Reevaluation of biopsy specimens using a monoclonal antibody against
CMV identified positive cells, although inclusion bodies were not found in hematoxylin and eosin sections. Finally,
the case was concluded to be synchronous onset of CMV colitis and UC.
Conclusion: Synchronous CMV colitis is not routinely investigated in newly diagnosed UC patients. Together with a
recent observation in animal studies, it is plausible that a subset (a few to several per cent) of UC patients develop
synchronous CMV infection. Further studies are needed to elucidate the plausibility.
Keywords: Cytomegalovirus, Ulcerative colitis, Cytomegalovirus colitis
Cytomegalovirus (CMV) is a ubiquitous agent that
asymptomatically infects the majority of persons [1,2].
Following infection, CMV remains lifelong in a latent
state. Therefore, most cases of symptomatic CMV infec-
tion are caused by reactivation of a latent virus. CMV
infection can occur in immunocompetent individuals,
but it most frequently occurs in immunocompromised
patients such as recipients of organ transplants, patients
undergoing hemodialysis, patients receiving immuno-
suppressive drugs, and patients with acquired immune
deficiency syndrome .
The association of CMV infection in severe cases of
ulcerative colitis (UC) is well known and the CMV infec-
tion in these cases should be treated with an antiviral
agent . Advances in diagnostic techniques for CMV
infection [4,5] have contributed to our understanding of
UC associated with CMV. Domenech et al. prospectively
studied the prevalence of CMV infection in five groups:
active UC requiring intravenous steroids (n=25), steroid-
refractory active UC treated with intravenous cyclospor-
ine (n=19), inactive UC on azathioprine (n=25), inactive
UC on mesalamine (n=25), and healthy controls (n=25)
. Only patients with steroid-refractory active UC (six
of 19 patients, 32%) were compromised with CMV infec-
tion . Using CMV antigenaemia assay and plasma
polymerase chain reaction, it was found that reactivation
of CMV up to 8 weeks after treatment with prednisolone
* Correspondence: firstname.lastname@example.org
1Division of Gastroenterology, Akita, Japan
Full list of author information is available at the end of the article
© 2013 Chiba et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Chiba et al. BMC Research Notes 2013, 6:40
and/or immunosuppressants such as cyclosporine was
common (52.1%, 25/48) in moderate to severe UC, and
CMV disappeared without antiviral therapy . In the
above cases, UC was diagnosed first, and CMV infection
was identified later.
In 2009, a trigger role of CMV and norovirus was
suggested in the development of UC and Crohn’s dis-
ease, respectively, in experimental murine systems [8-10].
Here, we report a case in which CMV colitis and UC
A 50-year-old woman underwent right partial mastec-
tomy for breast cancer in December 2007, after which
she was taking anastrozole (ArimidexR, AstraZeneca,
Osaka, Japan), an aromatase inhibitor, as preventive
therapy for breast cancer. There were no other relevant
hospitalizations or regular medications. She experienced
diarrhea for two days in late November 2009. Then a
high fever above 38 centigrade persisted, so she visited
the Outpatient Department for feverish patients (day 8).
A laboratory test for influenza was negative. The
following day, she visited the Division of Breast Surgery,
where an antibiotic was prescribed for suspected urinary
tract infection. Since the antibiotic was ineffective, she
visited the Department of Internal Medicine (day 12).
Abdominal ultrasonography revealed thickness of the
bowel wall ranging from the transverse to the descending
colon. She was referred and admitted to the Division of
Gastroenterology (day 14). Laboratory data on admission
showed elevated erythrocyte sedimentation rate (65 mm/
hr: normal range, <10 mm/hr), high C-reactive protein
(2.3 mg/dl: ≤0.3 mg/dl), elevated α2-globulin (11.5%: 4.8-
8.6%), mild anemia (hemoglobin 11.5 g/dl: 12.0-15.1 g/dl),
mild thrombocytosis (33.0 × 104/mm3:15.2-31.4 × 104/
mm3), and 2% atypical lymphocytes with the normal num-
ber of white blood cells (7000/mm3: 3900-8800/mm3). Al-
though there was no bloody stool, fecal occult blood was
over 1000 ng/ml (normal range <100 ng/ml). Colonoscopy
(day 15) showed diffuse inflammation without ulceration
in the entire large bowel and pseudomembranes in the sig-
moid colon (Figure 1A, B). The tentative diagnosis was
UC with antibiotic-associated pseudomembranous colitis.
Metronidazole 750 mg/day was started. Clostridium
difficile toxin was negative and stool culture did not re-
veal any pathogen including enterohemorrhagic E. coli,
Campylobactor jejuni, Salmonella species, Staphylococcus
aureus, and Krebsiella oxytoca. Histology of the colon
showed crypt abscesses consistent with UC. Therefore, a
diagnosis of UC was made and sulfasalazine, 3 g/day, was
started (day 22). The fever disappeared in a few days. Her
laboratory data improved week by week. Fecal occult blood
over 1000 ng/ml lasted until day 40. Fecal occult blood was
negative on day 47. Colonoscopy on day 57 confirmed a
morphological remission, and she was discharged on the
Reviewing her hospitalization, it was found that
positive CMV antigenaemia (2/150,000 polymorpho-
nuclear neutrophils: normal, no positive cells) tested
on day 20 had been missed. Therefore, paraffin em-
bedded colonic biopsy specimens were reevaluated
immunohistochemically using a monoclonal antibody
against CMV. Although inclusion bodies were not
found in hematoxylin and eosin sections, immu-
nohistologically positive cells were found in specimens
from the ascending and sigmoid colon (Figure 2A, B).
Disappearance of CMV antigenaemia and immunohis-
tologically positive cells was ascertained on day 114
and day 125 respectively. She has been in remission to the
present (September 2012).
Figure 1 Diffuse inflammation in the ascending colon (A) and pseudomembranes in the sigmoid colon (B).
Chiba et al. BMC Research Notes 2013, 6:40
Page 2 of 5
It is difficult to explain this case as being solely CMV
colitis. The most common endoscopic abnormality of
CMV colitis is multiple ulcers [11,12]. When whole
segments of colon are involved, lesions are skipped in
CMV colitis . In this case, ulcers were absent. The
lesion was not skipped but continuous and showed crypt
abscesses which are consistent with features of ulcerative
colitis. In addition, clinical response was obtained with
the drug for UC, sulfasalazine. Therefore, the present
case can be concluded to be an association of CMV
colitis and UC.
Initially this case was thought to be an atypical case of
UC in which a high fever instead of bloody stool was
manifested and pseudomembrane was observed in the
sigmoid colon. Fever is one of the predominant features
of CMV infection, and pseudomembrane has been
reported in CMV colitis [14,15]. Therefore, these atypical
phenomena can be explained by an involvement of
CMV infection (colitis).
When UC developed the patient was taking anastrozole,
aromatase inhibitor. Since hormone replacement therapy
is a protective against relapse in IBD , the use of
aromatase inhibitor which suppresses the production of
Figure 2 Positive cells in the ascending (x 400) (A) and sigmoid colon (x 200) (B) stained with monoclonal antibody
Table 1 Synchronous onset of cytomegalovirus colitis and ulcerative colitis
Age/ ChiefCMV Atypical HistologicalType of UC
Sex complaintinfectionlymphocyte diagnosis of by extent
Diepersloot et al., 1990 39/f F, HA, AP, BD primary+ IB, IHC, ISHP
Lortholary et al. 1993 27/f F, BDprimary5% IBLt
Orvar et al., 1993 33/f F, AP, BD, WLprimaryn.d. IB, IHCP
Mate del Tio et al., 1996  64/mBD, WL primary0 IB, IHC Lt
Aoyagi et al., 1998  41/f n.d.n.d.n.d. IB, IHCEC
Hussein et al., 2006  29/mF, AP, WDprimary43% IB: negativeEC
Martin et al., 2006 28/m F, AP, HA, BDprimary18%IBLt
Kim et al., 2010 19/m n.d.n.d. n.d. IHC Lt
33/mn.d.n.d. n.d. IHCEC
40/f n.d.n.d. n.d.IHCLt
Kim et al., 2012 58/mn.d.n.d.n.d. IHC EC
39/mn.d.n.d. n.d.IHC Lt
68/mn.d.n.d.n.d.IB, IHC Lt
Present case50/fFprimary 2%IHCEC
UC, ulcerative colitis; CMV, cytomegalovirus; f, female; m, male; F, fever; HA, headache; AP, abdominal pain.
BD, bloody diarrhea; WL, weight loss; WD, watery diarrhea; n.d., not described; IB, inclusion body.
IHC, immunohistochemistry; ISH, in situ hybridization; P, proctosigmoiditis; Lt, left-sided colitis, EC, entire colitis.
Chiba et al. BMC Research Notes 2013, 6:40
Page 3 of 5
estrogen might initiate IBD. However, no UC case
associated with anastrozole has been reported to date.
There is no UC case among 494 Japanese reports of ad-
verse effects of anastrozole between February 2001, when
the drug was started to be used in Japan, and December
2012 (Center of Medical Information, AstraZeneca,
Synchronous onset of CMV colitis and UC was first
reported in 1990 . Since then at least fifteen cases have
been reported by nine authors (Table 1) [18-25]. These
cases were primary infections rather than reactivation of
CMV. During a retrospective survey of the prevalence of
CMV colitis in UC by immunohistochemistry, Kim et al.
made an intriguing finding: identification of CMV colitis
in 8.2% (5/61) of newly diagnosed UC patients . None
of the five cases had inclusion bodies on hematoxylin and
eosin stain; consequently, none of them was diagnosed
with CMV colitis at the time of diagnosis of UC. This
means that a majority of synchronous CMV colitis is
missed in newly diagnosed UC patients in routine prac-
tice. As in Kim et al’s case , involvement of CMV col-
itis in the present case had been missed during her
De novo inflammatory bowel disease is an increasingly
recognized entity: de novo inflammatory bowel disease,
a more common UC than Crohn’s disease, develops after
solid organ transplantation . The incidence of de
novo IBD in the transplanted patients is estimated to be
ten times the expected incidence of IBD in the general
population . The main risk factor of de novo IBD
has been found to be CMV infection [27-30]. Onyeagocha
et al. investigated the significance of CMV infection on
the development of colitis in a murine system . Murine
CMV (MCMV) infection resulted in lasting elevation of
antibodies to gut commensal bacteria that is observed in
human IBD . Colitis developed following a trigger
(dextran sodium sulfate) in a far more severe form in
MCMV-infected mice than in mice treated by the trigger
alone. They concluded that (latent) CMV infection may
predispose to developing IBD.
We have reported a case in which CMV colitis and UC
synchronously developed. It is plausible that a subset (a
few to several per cent) of UC patients develop syn-
chronous CMV infection. Further studies are needed to
elucidate the plausibility.
Written informed consent was obtained from the patient
for publication of this case report and any accompanying
images. A copy of the written consent is available for
review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
MC is a responsible doctor for the patient, undertook barium enema study,
and wrote the report. ST performed colonoscopy. TA contributed to the
acquisition of data. IO performed microscopic studies. All authors read and
approved the final manuscript.
1Division of Gastroenterology, Akita, Japan.2Department of Pathology,
Nakadori General Hospital, Akita, Japan.
Received: 15 October 2012 Accepted: 30 January 2013
Published: 2 February 2013
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Cite this article as: Chiba et al.: Cytomegalovirus infection associated
with onset of ulcerative colitis. BMC Research Notes 2013 6:40.
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